Integrative mechanisms of mitral cells

二尖瓣细胞的整合机制

• 批准号: 6597579
• 负责人: Michael Thomas Shipley
• 金额: $ 22.85万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6597579
• 关键词: cellular polarity; genetically modified animals; laboratory mouse; membrane potentials; olfactions; olfactory lobe; tissue /cell preparation; voltage /patch clamp

The proposed research aims to elucidate the integrative mechanisms of olfactory bulb mitral cells, particularly as they relate to glomerular pattern analysis in the olfactory bulb. Two novel properties of mitral cells, membrane potential bistability and long lasting depolarizations (LLDs), are the specific focus of biophysical and pharmacological measurements to determine the underlying intrinsic currents and synaptic mechanisms producing these two properties of mitral cells. A novel slice preparation of early postnatal mouse brain which retains connections between olfactory neurons and olfactory bulb will be used to test specific hypotheses concerning the integrative functions of bistability and LLDs. Voltage clamp protocols will be used to characterize the activation and inactivation curves of intrinsic and synaptically activated currents in mitral cells elicited by antidromic stimulation of the lateral olfactory tract and orthodromic stimulation of the olfactory nerve. Dual intracellular recordings from the apical dendrite and soma of a mitral cell are proposed as are pairwise recordings from two mitral cells receiving input from the same glomerulus. Cross correlation techniques will be applied to test whether LLDs lead to synchronization of the mitral cell population with apical dendrites in the same glomerulus. Dual mitral cell recordings will also be used to test the hypothesis that bistability regulates the sensitivity of mitral cells to olfactory nerve inputs and functions as a temporal amplifier of lateral inhibition. The development of a viable olfactory bulb slice preparation from postnatal mouse makes possible the visualization of mitral cells with DIC/IR optics so that biophysical and integrative synaptic mechanisms can be made routinely with dual intracellular recordings. Normal and transgenic mice will be used to address questions of neurotransmitter receptor roles in mitral cell integrative mechanisms. Preliminary data show that the proposed techniques are working in the PI?s laboratory.

拟议的研究旨在阐明综合机制 嗅球二尖瓣细胞的含量，尤其是与肾小球相关的 嗅球中的模式分析。二尖瓣细胞的两个新型特性， 膜潜在的双重性和持久的去极化（LLD）是 生物物理和药理测量的特定重点，以确定 产生这两种的基本固有电流和突触机制 二尖瓣细胞的性质。早期产后小鼠的新型切片准备 保留嗅觉神经元与嗅球之间连接的大脑 将用于测试有关集成函数的特定假设 双重性和llds。电压夹具协议将用于表征 固有和突触激活的激活和灭活曲线 通过横向刺激引起的二尖瓣细胞中的电流 嗅觉神经的嗅觉和正排质刺激。双重的 二尖瓣细胞的顶端树突和躯体的细胞内记录是 提出了来自两个二尖瓣单元的成对记录，从 相同的肾小球。跨相关技术将应用于测试 LLD是否导致二尖瓣群体与顶端同步 同一肾小球中的树突。双二尖瓣记录也将使用 为了测试双尖态灵敏度的假设 细胞到嗅觉神经输入和功能作为侧面的时间放大器 抑制。从 产后小鼠可以使用DIC/IR可视化二尖瓣 光学元件使生物物理和综合突触机制 通常使用双重细胞内记录。正常和转基因小鼠将是 用于解决二尖瓣细胞中神经递质受体角色的问题 综合机制。初步数据表明，提出的技术是 在PI的实验室工作。